CYP7A1

cytochrome P450 family 7 subfamily A member 1, the group of Cytochrome P450 family 7

Basic information

Region (hg38): 8:58490178-58500163

Previous symbols: [ "CYP7" ]

Links

ENSG00000167910 ∙ NCBI:1581 ∙ OMIM:118455 ∙ HGNC:2651 ∙ Uniprot:P22680 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency (Supportive), mode of inheritance: Semidominant

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP7A1 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP7A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	23		31
missense			91	2	2	95
nonsense			1			1
start loss						0
frameshift	1		5			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2			2
splice region			5	3		8
non coding			3	13	8	24
Total	1	0	111	38	10

Highest pathogenic variant AF is 0.0000263

Variants in CYP7A1

This is a list of pathogenic ClinVar variants found in the CYP7A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-58491466-G-C		CYP7A1-related disorder	Likely benign (May 10, 2024)
8-58491468-CA-ATT			Uncertain significance (Jul 31, 2018)
8-58491470-T-C			Uncertain significance (Jan 27, 2017)
8-58491517-T-C			Uncertain significance (May 07, 2018)
8-58491521-G-A			Uncertain significance (Jan 15, 2022)
8-58491521-G-C		not specified	Uncertain significance (Nov 22, 2023)
8-58491529-G-A			Likely benign (Jan 12, 2023)
8-58491542-C-T			Uncertain significance (Feb 22, 2022)
8-58491543-G-A		not specified	Uncertain significance (Nov 17, 2022)
8-58491580-T-A			Likely benign (Oct 23, 2023)
8-58491581-A-G		CYP7A1-related disorder	Conflicting classifications of pathogenicity (Mar 16, 2021)
8-58491606-G-C			Uncertain significance (Dec 19, 2022)
8-58491608-A-G			Uncertain significance (May 02, 2017)
8-58491616-C-A			Uncertain significance (Oct 25, 2022)
8-58491633-C-T			Uncertain significance (Aug 10, 2016)
8-58491642-C-T			Uncertain significance (Mar 13, 2023)
8-58491656-G-A		CYP7A1-related disorder	Uncertain significance (Sep 02, 2024)
8-58491686-A-G		not specified	Uncertain significance (May 06, 2024)
8-58491689-T-G			Uncertain significance (Nov 24, 2024)
8-58491697-C-A		not specified	Uncertain significance (Oct 04, 2022)
8-58491698-T-C		CYP7A1-related disorder	Uncertain significance (Mar 25, 2016)
8-58491715-A-G			Likely benign (Feb 26, 2024)
8-58491741-C-T			Uncertain significance (Oct 05, 2023)
8-58491742-G-A			Benign/Likely benign (Nov 22, 2023)
8-58491750-CAA-C			Uncertain significance (Jul 17, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP7A1	protein_coding	protein_coding	ENST00000301645	6	10059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000245	0.984	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.459	292	271	1.08	0.0000148	3348
Missense in Polyphen		125	111.32	1.1228		1366
Synonymous	-0.0291	105	105	1.00	0.00000626	945
Loss of Function	2.13	9	19.0	0.472	0.00000100	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000243	0.000242
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000282	0.000281
Middle Eastern	0.000109	0.000109
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes a rate-limiting step in cholesterol catabolism and bile acid biosynthesis by introducing a hydrophilic moiety at position 7 of cholesterol. Important for cholesterol homeostasis. {ECO:0000269|PubMed:19965590}.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Bile secretion - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Primary bile acid biosynthesis - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Statin Pathway, Pharmacodynamics;27-Hydroxylase Deficiency;Bile Acid Biosynthesis;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;Drug Induction of Bile Acid Pathway;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Liver X Receptor Pathway;Vitamin D Receptor Pathway;PPAR Alpha Pathway;Farnesoid X Receptor Pathway;Nuclear Receptors Meta-Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Angiopoietin Like Protein 8 Regulatory Pathway;PPAR signaling pathway;Liver steatosis AOP;Oxidation by Cytochrome P450;Statin Pathway;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Endogenous sterols;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts via 27-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Metabolism of steroids;Bile acid biosynthesis;Steroids metabolism;bile acid biosynthesis, neutral pathway (Consensus)

Recessive Scores

• pRec: 0.672

Intolerance Scores

• loftool: 0.730
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.47

Haploinsufficiency Scores

• pHI: 0.727
• hipred: N
• hipred_score: 0.295

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.774

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cyp7a1
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: bile acid biosynthetic process;cholesterol catabolic process;sterol metabolic process;regulation of lipid metabolic process;cholesterol homeostasis;positive regulation of cholesterol biosynthetic process;negative regulation of fatty acid biosynthetic process;oxidation-reduction process;regulation of bile acid biosynthetic process;cellular response to glucose stimulus;cellular response to cholesterol
• Cellular component: endoplasmic reticulum membrane;organelle membrane;intracellular membrane-bounded organelle
• Molecular function: iron ion binding;cholesterol 7-alpha-monooxygenase activity;heme binding